1.A.4.5.7Cold-sensitive (opens with decreasing temperatures; e.g., <22°C) and menthol-sensitive cation-selective channel, transient receptor potential melastatin 8 (TRPM8). TRPM8 is activated by low temperatures and cooling agents such as menthol. It underlies the cold-induced excitation of sensory neurons. Its gating is regulated by voltage and lysophospholipids which induce prolonged channel opening (Vanden Abeele et al., 2006; Bautista et al., 2007; Matta and Ahern, 2007). It can be converted to an anion-selective channel by introducing a lysyl residue in TMS 6 (Kuhn et al., 2007). Gating of TRPM8 channels is activated by cold and chemical agonists in planar lipid bilayers (Zakharian et al., 2010). Residues involved in intra- and intersubunit interactions have been identified, and their link with
channel activity, sensitivity to icilin, menthol and cold, and their impact on channel oligomerization have been measured (Bidaux et al. 2015). Targeting the small isoform of TRPM8 may be useful to fight prostate cancer (Bidaux et al. 2016). The human isoform is 83% identical to the TRPM8 of the collared flycatcher (TC# 1.A.4.5.13), the structure of which has been characterized to 4.1 Å resolution (Yin et al. 2018).